DEPENDENCY OF SYNTHESIS OF 2,3-DIPHOSPHOGLYCERATE IN HUMAN ERYTHROCYTES ON CONCENTRATION OF ADP

The spontaneous decrease in 2,3-diphosphoglycerate (2,3-DPG) concentration in human erythrocytes incubated in the presence of glucose is markedly delayed or completely prevented by dipyridamole (5·10-4 M). This effect is not due to an inhibition of 2,3-DPG phosphatase, since it is abolished after interruption of 2,3-DPG synthesis. The effect of dipyridamole therefore can only be explained by an increase in 2,3-DPG formation. This increase was shown to be causally related to a diminution of ADP in the presence of dipyridamole. Since red cell glycolysis remained unchanged under these conditions, the decrease in ADP should result in an increase of 1,3-DPG concentration. The elevation of 1,3-DPG, in turn, gives rise to an enhancement of 2,3-DPG synthesis, which is responsible for the observed effect of dipyridamole on 2,3-DPG metabolism. The amount of glucose metabolized by the 2,3-DPG cycle in intact red cells under physiological conditions depends on the concentration of ADP. As ADP concentration diminishes from 0.12 to 0.07 μMol/ml erythrocytes, the proportion of glucose degraded via 2,3-DPG increases from 15 to 22%. Possible mechanisms of the action of dipyridamole on the ADP level in erythrocytes are discussed. © 1969 Springer-Verlag.